Background:  Male circumcision has been associated with reduced rates of genital ulcer disease, and this might in part explain the protective effects of circumcision on HIV acquisition. The effects of circumcision on urethral infections are unclear.

Methods:  A Ugandan randomized trial enrolled 4996 uncircumcised HIV-negative men aged 15 to 49, who agreed to receive their HIV results and counseling. Men were randomized to immediate circumcision (2474), or circumcision delayed for 24 months (2522), and followed at 6, 12, and 24 months. At each visit, participants were asked about symptoms suggestive of sexually transmitted infections—including genital ulcer disease, urethral discharge, and dysuria—during the preceding follow-up interval. We determined the period prevalence of sexually transmitted infection symptoms per 100 visits and estimated prevalence rate ratios (PRR) of sexually transmitted infection symptoms in circumcised versus uncircumcised men using log-binomial regression with robust variance. HIV incidence was also assessed and incidence rate ratios (IRR) with robust standard errors were estimated by Poisson regression.

Results:  The period prevalence of genital ulcer disease was 3.1% in the circumcised and 5.8% in the uncircumcised men over all follow-up visits (PRR = 0.53, 95%CI 0.43 to 0.64, p <0.0001).  The rates of urethral discharge were 1.8% in the circumcised and 2.2% in the uncircumcised men (PRR = 0.84, 95%CI 0.63 to 1.11, p = 0.21), and rates of dysuria were 3.2% and 3.3% in the intervention and control arms, respectively (PRR = 0.97, 95%CI 0.77 to 1.21). Genital ulcer disease was associated with increased risk of HIV acquisition, but circumcision was protective irrespective of genital ulcer disease.  Compared to circumcised men without genital ulcer disease (HIV incidence 0.63/100 person-years), the incidence was 1.06/100 person-years in uncircumcised men without genital ulcer disease (IRR = 1.67, 95%CI 0.96 to 2.91), 1.82/100 person-years in circumcised men with genital ulcer disease (IRR = 2.87, 95%CI 0.67 to 12.34), and 6.32/100 person-years (IRR = 9.97, 95%CI  4.87 to 20.39) in uncircumcised men with genital ulcer disease.

Conclusions:  Male circumcision reduced symptomatic genital ulcer disease, but had no effect on urethral symptoms. The reduction in genital ulcer disease associated with circumcision partly accounts for the protective effect of circumcision against HIV infection.